The purpose of this investigation was to determine the effect of a lithogenic diet (one which is known to cause gallstones in hamsters) on the activity of HMG CaA reductase, the rate limiting enzyme in the synthesis of cholesterol. Syrian hamsters were either fed a normal diet or a lithogenic diet and then at various periods were killed. The activity of hepatic HMG CoA reductase was determined. Increases in the activity of HMG CoA reductase were found early in hamsters on the lithogenic diet and cholesterol gallstones developed later. The elevation of this enzyme is indicative of increased synthesis as a responsible factor in the genesis of cholesterol gallstones in these hamsters. BIBLIOGRAPHIC REFERENCE: Ginsberg, Ronald L., Duane, William C., and Flock, Eunice V.,: Hepatic 3-Hydroxy-3-Methylglutaryyl CoA Reductase Activity in Hamsters on a Lithogenic Diet. J. Lab. Clin. Med. 89:928-936, 1977.